Suppression of lymphocyte responses by cephalosporins.

Human peripheral blood lymphocytes were cultured in several concentrations of each of several cephalosporins. Responses to phytohemagglutinin were compared with that of duplicate cultures containing penicillin-streptomycin, chloramphenicol, or no antibiotics. Possible effects of cephalosporins on responses of lymphocytes to concanavalin A and pokeweed mitogen were similarly determined. Significant suppression of responses to phytohemagglutinin and concanavalin A were seen in cultures containing 50 microgram each of cephalothin, cephalexin, or cephradine per ml. Lymphocyte responses to pokeweed mitogen were suppressed by 50 microgram of cephalexin, cephradine, or cefoxitin per ml. A higher concentration (100 microgram/ml) of all cephalosporins except cefoxitin and cefazolin suppressed the phytohemagglutinin response to less than 20% that of controls. Chloramphenicol (50 microgram/ml) did not inhibit the response to any mitogen used. These findings suggest that cephalosporins should not be used for prevention of bacterial overgrowth in certain cell cultures. Since many of the cephalosporins were suppressive in therapeutically attainable concentrations, these results may have potential clinical significance.     

Cytotoxic activity against rubella-infected cells in the supernatants of human lymphocyte cultures stimulated by rubella virus.

Supernatant fluids of lymphocyte cultures from rubella-seropositive donors, stimulated with inactivated rubella virus, showed cytotoxic activity against rubella-infected target cells (NYU 32 line of human embryonic fibroblasts) but not against uninfected fibroblasts. The time of appearance of cytotoxic activity in rubella-stimulated lymphocyte cultures correlated with increased rate of DNA synthesis as measured by thymidine uptake. No such cytotoxic activity became detectable in the supernatants of lymphocyte cultures from rubella-seronegative donors cultured in the presence of rubella virus, or in unstimulated lymphocyte cultures from seropositive or seronegative donors. The cytotoxic activity was lost at 60degreesC in 30 min. In contrast to this rubella virus-induced cytotoxic activity, cytotoxin produced in mitogen-stimulated lymphocyte cultures from rubella seropositive and seronegative donors was equally cytocidal against rubella-infected and uninfected human fibroblasts. Although the nature of cytotoxic activity remains to be characterized, it is suggested that it is associated with a lymphokine released immune-specifically from rubella virus-stimulated lymphocytes.     

Cyclosporin A inhibits lymphokine production but not the responses of macrophages to lymphokines.

Cyclosporin A (Cs A) exerted a dose-related inhibitory effect on antigen (ovalbumin, OVA) and phytohaemagglutinin (PHA)-induced transformation of guinea-pig lymph node cells (LNC). Whereas 0.05 micrograms/ml was sufficient to depress these responses markedly, it required 100-fold this concentration of Cs A to inhibit the production of lymphocyte activating factor (LAF) by lipopolysaccharide (LPS) stimulated peritoneal macrophages. Addition of Cs A together with insoluble concanavalin A (iCon A) to LNC cultures resulted in suppressed lymphokine production, as assessed by measurement of migration inhibition factor (MIF), the generation of macrophage procoagulant activity (MPCA) and the release of lymphocyte-derived-macrophage chemotactic factor (LDCF). Cs A also inhibited MIF and procoagulant production by sensitized peritoneal exudate cells in response to antigen, at the same concentrations which blocked lymphocyte transformation. In contrast, Cs A had no direct effect on the migration of peritoneal cells from capillary tubes, or on the responses of macrophages to preformed MIF, the lymphokine inducing MPCA or LDCF. Overnight incubation of macrophages with Cs A did, however, result in mild inhibition of their basal level of procoagulant activity.     

Thymosin effects on immunoglobulin synthesis and suppressor T cell activity in normal subjects and patients with primary biliary cirrhosis

Peripheral blood lymphocytes from patients with primary biliary cirrhosis previously have been reported to demonstrate reduced pokeweed mitogen-stimulated immunoglobulin synthesis and diminished function of suppressor T cells. To determine whether thymic hormone preparations reverse these immunologic defects in vitro, the effects of thymosin fraction 5 and thymosin alpha 1 on immunoglobulin synthesis and concanavalin A-induced suppression of immunoglobulin synthesis were investigated in normal subjects and patients with primary biliary cirrhosis. In normal subjects, no effects of thymosin were observed on unstimulated and pokeweed mitogen-stimulated immunoglobulin synthesis, nor on Con A-induced suppressor cell activity. Lymphocytes from patients with PBC synthesized less IgG and IgM than normals when stimulated by pokeweed mitogen, and this difference was enhanced by both thymosin fraction 5 and thymosin alpha 1. Con A suppression of immunoglobulin synthesis was abnormal in only one PBC subject so that thymosin effects on impaired suppressor T cell activity could not be tested.     

Activation of macrophages by products of lymphocytes from normal and syphilitic rabbits.

The production of soluble macrophage-activating factors by lymphocytes from syphilitic and normal rabbits was examined. Culture supernatants of splenic lymphocytes cultured with Treponema pallidum antigens or concanavalin A were incubated with rabbit peritoneal macrophages in vitro. The macrophage monolayers were then washed and infected with log-phase Listeria monocytogenes. Activation of the macrophages by lymphocyte products was measured by the ability of the macrophages to resist intracellular multiplication of Listeria and thus survive infection. Macrophages incubated with supernatants of unstimulated lymphocytes or T. pallidum-stimulated lymphocytes from normal rabbits were unable to resist intracellular multiplication of Listeria. Specifically stimulated lymphocytes from syphilitic rabbits and mitogen-stimulated lymphocytes from both normal and syphilitic rabbits demonstrated a clear ability to produce soluble factors which conferred upon macrophages the ability to limit the intracellular growth of the bacteria. Antigen or mitogen alone was unable to activate the macrophages; the presence of lymphocyte products was required.     

Mononuclear cell function in Mycobacterium tuberculosis infected guinea pigs

In this study mononuclear cell function was studied in the lymph glands, spleen, and peripheral blood of Mycobacterium tuberculosis infected guinea pigs. Adherent cells from draining lymph nodes and spleens of infected animals spontaneously produced a factor which inhibited normal lymphocyte proliferative responses. As it has previously been shown that this factor activates a population of suppressor T cells, resident lymphocytes in the lymph nodes and spleen were examined and were shown to inhibit normal lymphocyte functions. It is suggested that adherent cells ingesting M. tuberculosis spontaneously release a suppressor cell activating factor (SCAF) which locally activates lymphocytes to become suppressor cells. Even at a time of overwhelming infection, peripheral blood adherent cells could not be shown to release SCAF and peripheral blood suppressor cells could not be identified. Although peripheral blood lymphocyte proliferative responses to PHA were normal in infected animals, their ability to produce the lymphokine macrophage inhibition factor was considerably reduced after the second week of infection. This dissociation between lymphocyte proliferation and lymphokine production is similar to that previously described in humans overwhelming tuberculosis.     

Cross-reactivity of cefotetan and ceftriaxone antibodies,associated with hemolytic anemia,with other: cephalosporins and penicillin

Most drug-induced immune hemolytic anemias since the late 1980s have been caused by the second- and third-generation cephalosporins, cefotetan and ceftriaxone, respectively. Cross-reactivity of cefotetan and ceftriaxone antibodies with other cephalosporins or penicillin has been studied only minimally. We tested 7 serum samples previously identified to contain cefotetan antibodies and one serum sample previously identified to contain ceftriaxone antibodies against 9 other cephalosporins, penicillin, and 7-aminocephalosporanic acid in the presence of RBCs and also used hapten inhibition to indicate cross-reactivity. Serum samples containing cefotetan antibodies showed some cross-reactivity with cephalothin and cefoxitin (and to a much lesser extent with penicillin and ceftazidime). The ceftriaxone antibodies showed very weak cross-reactivity with cefotaxime, cefamandole, and cefoperazone. There was very little cross-reactivity between cefotetan antibodies and the drugs tested in the present study. We have no data to determine whether the in vitro data relate to in vivo reactivity.     

Pulmonary and systemic immunoregulatory changes during the development of experimental asbestosis.

Initial studies on the effects of low dose exposure to asbestos on pulmonary and systemic immune responses have revealed a bi-phasic pattern characterized by an early enhancement followed by inhibition of lymphocyte responses to several mitogens. In the present study, we sought to define the cellular and humoral factors, responsible for the observed effects. The early enhancement of peripheral blood and pulmonary lymphocyte responses to mitogens may be due, at least in part, to the loss of the inhibitory capacity of alveolar macrophages from asbestos exposed animals to suppress lymphocyte response. Furthermore, macrophages from low dose exposed animals actually enhanced lymphocytes responses to Con A and PHA. The latter inhibition observed following 6-12 months of exposure may be due to the in vivo generation of suppressor lymphocytes. Unfractionated lymphocytes from blood or alveolar space as well as enriched T cells from high dose exposed animals suppressed the proliferative responses of pulmonary or circulating lymphocytes to PHA and Con A, but not to PWM. Similarly, pre-incubation of normal blood or pulmonary lymphocytes in serum from high dose exposed animals for 24 h induced the appearance of suppressor cell activity in these populations when further tested in a co-culture assay with normal fresh lymphocytes. Taken together, these studies demonstrate the multi-faceted effects of asbestos on the immune system. The eventual fibrogenic process of asbestosis may result from the interplay of several mechanisms, some of which are suggested in this work.     

Regulation of lymphocyte proliferation by cholesterol: the role of endogenous sterol metabolism and low density lipoprotein receptors

Cholesterol availability is a major determinant of the capacity of lymphocytes to proliferate. Either endogenously-synthesized cholesterol or that taken up from the medium can be utilized as a source for new membrane biosynthesis. Mitogenic stimulation of human lymphocytes augments the rate of endogenous sterol synthesis. This mitogen-induced increase in lymphocyte sterol synthesis can be observed within 4 h of stimulation and is prevented by suppressing the activity of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase with the specific inhibitors ML-236B or mevinolin. The resultant inhibition of lymphocyte sterol synthesis does not affect mitogen-stimulated blast transformation or initial entry into the S phase of the cell cycle, even when no source of exogenous sterol is present. However, maximal enlargement of the stimulated blast cells is suppressed by inhibition of HMG-CoA reductase activity, and lymphocyte proliferation is completely prevented. These inhibitory effects are reversed by the addition either of mevalonate, the product of the inhibited enzyme, or of low-density-lipoprotein (LDL) cholesterol. The finding that LDL cholesterol could not support growth of lymphocytes obtained from individuals who lacked LDL receptors indicates that LDL-mediated delivery of exogenous sterols to proliferating lymphocytes requires intact LDL receptors. The data indicate that neither endogenous sterol synthesis nor a source of cholesterol is necessary for mitogen-stimulated activation and blast transformation of human lymphocytes. Subsequent enlargement and cell division requires either sterol synthesis or an exogenous source of cholesterol. When the exogenous source of cholesterol is in the form of LDL, normal LDL receptors are also necessary.     

Suppression of lymphocyte adenosine 3′ : 5′-cyclic monophosphate (cAMP) by delta-9-tetrahydrocannabinol

Delta-9-tetrahydrocannabinol (THC) is the major psychoactive component of marijuana. Suppression of mitogen-stimulated blastogenesis of human lymphocytes in vitro by THC was previously demonstrated. This effect was shown to be concentration dependent with the non-toxic concentrations 5, 7.5, and 10 μg THC/ml showing the greatest suppression. However, the mechanism(s) by which THC induces suppression are still unclear. The current study examines the effect of THC on the adenosine 3′ : 5′-cyclic monophosphate (cAMP) pathway second messenger system, which is involved in activation of human peripheral blood lymphocytes. Lymphocyte cAMP levels were stimulated using three hormone receptor stimulators, isoproterenol, histamine, or 5′-N-ethylcarboxamide adenosine (NECA), each of which utilizes a different receptor to enhance cAMP production. THC suppressed cAMP levels independently of the hormone and receptor utilized. Levels of cAMP in non-mitogen-stimulated peripheral blood mononuclear cells and plastic non-adherent lymphocytes, as well as cells stimulated with phytohemmagglutinin, were suppressed by THC. Suppression of cAMP production by THC was further examined to determine whether inhibition involved a GTP-binding protein (G_i), which is known to down-regulate cAMP production. Cells were pre-treated with pertussis toxin to inhibit G_i activity; this blocked the THC-induced suppression of cAMP production. These results suggest that THC can exert its effects on second messenger systems at the lymphocyte membrane level, and that a pertussis toxin-sensitive G_i protein may be involved. Thus, second messenger regulated pathways may be involved in THC-induced immune suppression. However, the relationship between alteration of cAMP production and suppression of lymphocyte function due to the presence of THC in the medium remains to be established.     

Alkaline phosphatase activity is expressed only in B lymphocytes committed to proliferation.

Alkaline phosphatase (APase) activity was measured in murine splenic lymphocytes stimulated with the T lymphocyte mitogens phytohemagglutinin (PHA) and Concanavalin A (Con A) and the B lymphocyte mitogens lipopolysaccharide (LPS) and anti-immunoglobulin (anti-Ig). APase activity was found to be enhanced specifically in mitogen-stimulated B lymphocytes, but not in T lymphocytes. This enhancement starts around 8 h after stimulation with a mitogen. With soluble anti-Ig it was observed that the B cells enter G1 phase as assessed by RNA synthesis and blast transformation. However, these cells fail to synthesize DNA and also do not show any increase in APase activity. When the same anti-Ig coupled to Sepharose was used as a stimulator, cells synthesized DNA and also showed significant increase in APase activity. When hydroxyurea was added, the enhancement in APase activity by the mitogen was not diminished although the cells failed to synthesize DNA. These observations indicate that APase activity is enhanced only in activated B cells committed to proliferation.     

Chronic lymphocytic leukaemia. Studies on mitogen-stimulated lymphocyte interferon as a new technique for assessing T lymphocyte effector function

The present study employs a new technique for the study of human T-cell effector function in patients with chronic lymphocytic leukaemia: mitogen-stimulated interferon. Cultures of macrophages, T cell-enriched lymphocytes, or macrophages and lymphocytes combined were prepared from the blood of fourteen normal donors and five patients with chronic lymphocytic leukaemia. The effects of the mitogens, phytohaemagglutinin and pokeweed, on interferon production and lymphocyte transformation were studied and the following observations made: (a) T-cell effector and proliferative functions were depressed as evidenced by the absence of interferon and proliferative response to PHA and PWM at 3 days in vitro; (b) Three out of five patients showed no interferon or proliferative response at 6 days, thus indicating a B lymphocyte abnormality as well; (c) macrophages from both normal and leukaemic subjects augmented mitogen-stimulated lymphocyte interferon production and lymphocyte transformation. However, the addition of normal allogeneic macrophages to cultures of lymphocytes prepared from the patients did not restore the proliferative and interferon responses to normal levels.     

Suppression of delayed-type hypersensitivity reactions and lymphokine production by cyclosporin A in the mouse.

Two consecutive daily i.m. injections of cyclosporin A (Cs A) (greater than 50 mg/kg) inhibited delayed type hypersensitivity (DTH) responses in mice immunized with SRBC. Maximal suppression was observed when Cs A was administered 24 and 48 h after sensitization. Culture of spleen cells from these animals with antigen, insoluble concanavalin A (iCon A) or PHA revealed inhibition of the production of two lymphokines: that inducing macrophage procoagulant activity (MPCA) and macrophage chemotactic factor (LDCF). The inhibitory effect on lymphokine production was not due to depletion of T cells. In vitro, 25 ng/ml Cs A suppressed T cell proliferative responses to antigen and mitogen but much higher doses were required to impair the response to LPS. Similar doses of Cs A also suppressed lymphokine production, but the responses of macrophages to these lymphokines was unaffected, even at doses which totally inhibited lymphokine production. Production of interleukin 1 by LPS stimulated macrophages was inhibited by Cs A only at concentrations much greater than those required to suppress lymphokine production.     

Cell-mediated immunity to cytomegalovirus (CMV) and herpes simplex virus (HSV) antigens in the acquired immune deficiency syndrome: Interleukin-1 and interleukin-2 modifyin vitro responses

Peripheral blood lymphocytes (PBL) were obtained from five patients with the acquired immune deficiency syndrome (AIDS), six homosexual males with lymphadenopathy, and five normal heterosexual controls. Modulation of virus-specific immunity was assayedin vitro by measuring the lymphocyte blastogenic response and the production of lymphokine (leukocyte inhibition factor; LIF) by PBL stimulated with herpes simplex virus (HSV) or cytomegalovirus (CMV) antigens in the presence or absence of interleukin-1 (IL-1) and interleukin-2 (IL-2). PBL from the control and lymphadenopathy subjects responded to both antigens in the lymphocyte transformation assay (LT) measured on day 7, and the responses were significantly enhanced in cultures grown in the presence of antigen and IL-2 (1 U/ml). PBL from the AIDS patients were unresponsive, but responsiveness was restored by the addition of IL-2. The addition of IL-1 (0.02 µg/ml) to antigen-stimulated PBL cultures failed to enhance the proliferative responses in all three study groups. LIF production was assayed in the supernatants from day 1 PBL cultures. LIF was not produced by PBL from AIDS patients grown in the presence of viral antigens, whereas three of five patients from the lymphadenopathy group, and three of five control subjects gave rise to positive responses. The addition of IL-1 to the antigenstimulated cultures enhanced LIF production in the control and lymphadenopathy groups but not in the AIDS patients. The addition of IL-2 did not modulate LIF production by antigen-stimulated PBL from the control oR AIDS patients while suppressing the LIF response of the similarly stimulated PBL from the lymphadenopathy patients.     

In vitro X-ray irradiation of human peripheral blood T lymphocytes enhances suppressor function

We studied the effect of in vitro X-ray irradiation on human peripheral blood T lymphocytes, with regard to their suppressor activity related to the concanavalin A (Con A)-induced suppressor system. To generate suppressor T lymphocytes, purified human T lymphocytes were incubated for 3 days in the first culture, with or without Con A. These lymphocytes were irradiated with various doses of X-ray before, mid or after the culture. After doing a second culture for 6 days, we measured the suppressive influence of these cells on T lymphocyte proliferation rates stimulated with allogeneic mononuclear cells, and B lymphocyte proliferation rates stimulated with pokeweed mitogen. Irradiation (1,000 rad) of cultures to which Con A had not been added induced much the same level of suppressor activity as seen in the cultures with Con A. The suppressor activity gradually increased with lapse of time from the irradiation to the suppressor cell assay. Suppressor T lymphocytes were resistant to X-ray irradiation and independent of DNA synthesis. On the other hand, irradiation-induced enhancement was minimal in cultures incubated with Con A, regardless of the irradiation time. As irradiation of human peripheral blood T lymphocytes was found to induce a suppressor function in vitro, clinical and experimental applications of irradiation in cases of a suppressed T lymphocyte function may be feasible.     

B lymphocyte function in patients with rheumatoid arthritis: impact of regulatory T lymphocytes and macrophages--modulation by antirheumatic drugs

The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells. Synovial fluid mononuclear cells did not produce immunoglobulins in cultures stimulated with PWM, unless synovial T cells were removed and replaced with autologous blood T cells. Under these conditions synovial fluid B lymphocytes were induced by PWM to considerable IgG synthesis; fewer cells secreted IgM and IgA. About 8-9% of the induced IgM- and IgG-synthesizing cells displayed rheumatoid factor activity. Aurothiomalate markedly inhibited PWM-induced immunoglobulin production by normal lymphocytes cultured in vitro, probably by affecting monocyte/macrophage-lymphocyte interactions. The drug also had a direct inhibitory action on B lymphocytes, whereas T cells were resistant.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mitogen responses and interferon production after exposure of human macrophages to infectious and inactivated influenza viruses

Human macrophages were exposed to two influenza A viruses representing different subtypes. The donors were likely to have been exposed to one subtype (H3N2) but not to the other (H0N 1). Similar effects upon the macrophages were observed for both subtypes: macrophage enhancement of mitogen-stimulated lymphocyte transformation responses was depressed, and the macrophages produced interferon. In contrast, macrophages exposed to inactivated virus exhibited normal enhancement of lymphocyte transformation response, yet produced interferon, although in lower titers than did macrophages exposed to infectious virus.     

Theoylline Induced Non Specific Suppressor Activity in Human Peripheral Blood Lymphocytes

It is wellknown that theophylline yields phenotypic changes on suppressor cells. In the present study we investigated the possibility that theophylline could directly induce a suppressor activity on a lymphocyte subpopulation. We observed that a short preincubation (120 min at 37°C) with theophylline (1mM) activates human peripheral blood lymphocytes to suppress mitogenic response of autologous cells. This activity was not evident on a T cell subpopulation depleted of theophylline-sensitive (T-sens) lymphocytes.

Theophylline mediated suppressor activity is only present in the Concanavalin A stimulated cultures, thus suggesting a synergism between Concanavalin A and theophylline in the expression of non specific suppression. Moreover we observed that after a 24 hrs preincubation of lymphocytes in complete culture medium there was a complete loss of theophylline-induced suppression. Such a preincubation time also produced a decrease in the theophylline-mediated enhancement of intracellular 3',5' cyclic adenosine monophosphate levels and the impairment of E-rosette formation, suggesting that theophylline acts mainly on a “short-lived” suppressor lymphocyte subset.     

Detection of different macrophage-activating factor and interferon activities in supernatants of chicken lymphocyte cultures

Chicken spleen lymphocytes were cultivated under various conditions in order to produce and characterise functionally avian lymphokines. Biological properties of lymphokine-containing culture supernatants were evaluated with regard to their antiviral activity and their effects on cultured bone marrow-derived chicken macrophages, including induction of cytostatic activity, enhancement of phagocytic activity towards vital Candida albicans, and giant cell formation. Optimal doses of concanavalin A (ConA) for stimulation of lymphocytes varied between 2.5 and 40 mug/ml, depending on the cell concentration and presence or absence of serum. Lymphokine production occurred even without exogenous mitogen stimulation when cells were cultured at sufficiently high concentrations (1 to 2 x 10(7) cells/ml). Cytostasis-inducing capacity of lymphokine preparations against lymphoblastoid MDCC-RP1 cells was always combined with the presence of antiviral activity. Experimental results suggested that these two activities had to be attributed to at least two distinct lymphokines, i.e. macrophage-activating factor and interferon (IFN). ConA stimulation of lymphocytes from a single donor appeared to be the appropriate signal for production of IFN-gamma. Endogenous stimulation in mixed lymphocyte cultures more appropriately triggered production of IFN-alpha or IFN-ss, although production of IFN-gamma was not completely suppressed. Phagocytic activity of macrophages could also be increased by a cyto-kine present in conditioned media from confluent cultures of chicken embryo fibroblasts, chicken kidney cells, or bone marrow-derived chicken macrophages. In lymphokine preparations, this mediator may-even be a cofactor necessary for induction of multinucleated giant cell formation of cultured macrophages.     

Selective suppression of lymphokine production by human hybridoma suppressor factor (HSF)

We have made a human thymus cell hybridoma that secretes an immunosuppressive monoclonal lymphokine, referred to as hybridoma suppressor factor (HSF). This factor modulates the function of CD4+ cells suppressing their IL-2 production and suppressing PWM-induced B cell differentiation into Ig producing cells. Here we have examined the effect of HSF on the generation of T cell-derived lymphokines that regulate B cell growth and differentiation as well as the expression of other proteins involved in the control of T cell growth i.e., the p55 chain of the IL-2R and the transferrin receptor (TFR). HSF suppressed IFN-gamma activity produced by mitogen-stimulated PBMC without affecting the generation of lymphokines responsible for BCGF and BCDF activities. Additionally, HSF did not inhibit the expression of either IL-2R (p55) or TFR by activated T cells in spite of causing the suppression of IL-2 production. This evidence was further supported by experiments in which HSF selectively suppressed the accumulation of IL-2 mRNA without affecting IL-2R (p55) mRNA expression in mitogen-stimulated PBMC. The selective action of HSF may help to clarify the regulatory mechanisms involved in lymphokine gene expression as well as provide a way by which immune responses involved in autoimmunity and transplant rejection may be interrupted.